Organic matter accumulation and preservation in Alaskan continental margin sediments

Thesis (Ph.D.) University of Alaska Fairbanks, 1998Continental margin sediments provide a historical record of the sources and fate of organic matter (OM) originating both from the continents and from primary productivity in the overlying water column. However, since this record can be altered by microbial decomposition within the sediment, the history cannot be interpreted without understanding how decomposition can affect OM composition. Also, the margins accumulate much of the OM buried in ocean sediments; hence, knowledge of processes influencing preservation of OM in these sediments is essential to understanding the global carbon cycle. OM preservation was examined using two approaches. First, I studied sediments in the northeastern Gulf of Alaska to determine sources of OM and temporal changes in carbon accumulation. A large amount of OM, 45--70 x 104 tons/yr, accumulated in this region, about 50% from terrestrial sources. Most of the sediment cores showed little evidence of change in TOC, TN, or C and N stable isotope compositions due to decomposition within the sediment. Second, I investigated the processes that control OM preservation, focusing on the role of the OM adsorption to mineral surfaces. Because proteins are major constituents of sedimentary OM, I examined factors controlling their adsorption, decomposition, and preservation. Three hydrophilic proteins were strongly adsorbed by two clay minerals, an iron oxide, sub-oxic sediments from Resurrection Bay (RB), Alaska, and anoxic sediments from Skan Bay (SB), Alaska. The partition coefficients were large enough to lead to their preservation provided that the proteins did not decompose while adsorbed. Generally, adsorption of proteins to solid phases decreased decomposition rates, suggesting that adsorption is important in protecting these compounds from microbial attack. Greater protein decomposition rates were found in SB than in RB sediments, indicating that anoxia did not inhibit protein biodegradation. Naturally-occurring adsorbed proteins were extracted from SB and RB sediments using a detergent solution. Most of these adsorbed proteins were small (<12 kDa), indicating that only the proteins adsorbed within the micropores of particle surfaces are preserved long-term

A 2-step penalized regression method for family-based next-generation sequencing association studies

Large-scale genetic studies are often composed of related participants, and utilizing familial relationships can be cumbersome and computationally challenging. We present an approach to efficiently handle sequencing data from complex pedigrees that incorporates information from rare variants as well as common variants. Our method employs a 2-step procedure that sequentially regresses out correlation from familial relatedness and then uses the resulting phenotypic residuals in a penalized regression framework to test for associations with variants within genetic units. The operating characteristics of this approach are detailed using simulation data based on a large, multigenerational cohort

Case report: SAF-189s is a potent inhibitor in a lorlatinib-resistant NSCLC patient with acquired compound mutations ALK L1196M and D1203N

Acquired anaplastic lymphoma kinase (ALK) mutation is the major resistant mechanism to ALK tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients. At present, treatment options after acquiring secondary ALK mutations are still limited. Here, we report on a patient with metastatic ALK-rearranged NSCLC who was sequentially treated with ALK TKIs, from crizotinib to lorlatinib, and developed rare acquired compound ALK mutations (L1196M and D1203N) that confer resistance to lorlatinib. Moreover, our report describes the clinical response of an NSCLC patient with these compound mutations to multiple anti-tumor therapies. Among them, the patient was treated with SAF-189s 120 mg daily and had a stable disease lasting 3 months. Chemotherapy (pemetrexed-carboplatin) combined with bevacizumab was then administered. She achieved a partial response, which was maintained for 7 months as the best response. Since both SAF-189s and chemotherapy have shown a clear antitumor effect, they may be viable therapeutic options for these patients. Thus, our study can provide some reference in the treatment of NSCLC patients with ALK L1196M/D1203N compound mutations

The jet formation mechanism of Gamma-ray Narrow-line Seyfert 1 Galaxies

Under the coronal magnetic field, we estimate the maximal jet power of the Blandford-\Znajek (BZ) mechanism, Blandford-\Payne (BP) mechanism, and hybrid model. The jet power of the BZ and Hybrid model mechanisms depends on the spin of a black hole, while the jet power of the BP mechanism does not depend on the spin of a black hole. At high black hole spin, the jet power of the hybrid model is greater than that of the BZ and BP mechanisms. We find that the jet power of almost all gamma-\ray narrow line Seyfert 1 galaxies (gamma-\NLS1s) can be explained by the hybrid model. However, one source with jet power 0.1~\1 Eddington luminosity can not be explained by the hybrid model. We suggest that the magnetic field dragged inward by the accretion disk with magnetization-\driven outflows may accelerate the jets in this gamma-\NLS1.Comment: 9 pages,6 figures,accepted for publication in MNRA

General Physical Properties of Gamma-Ray-emitting Radio Galaxies

We study the radio galaxies with known redshift detected by the Fermi satellite after 10 years of data (4FGL-DR2). We use a one-zone leptonic model to fit the quasi-simultaneous multiwavelength data of these radio galaxies and study the distributions of the derived physical parameter as a function of black hole mass and accretion disk luminosity. The main results are as follows. (1) We find that the jet kinetic power of most radio galaxies can be explained by the hybrid jet model based on ADAFs surrounding Kerr black holes. (2) After excluding the redshift, there is a significant correlation between the radiation jet power and the accretion disk luminosity, while the jet kinetic power is weakly correlated with the accretion disk luminosity. (3) We also find a significant correlation between inverse Compton luminosity and synchrotron luminosity. The slope of the correlation for radio galaxies is consistent with the synchrotron self-Compton (SSC) process. The result may suggest that the high-energy component of radio galaxies is dominated by the SSC process.Comment: 9 pages,7 figures, accept for publication in ApJ

MATH5 controls the acquisition of multiple retinal cell fates

Math5-null mutation results in the loss of retinal ganglion cells (RGCs) and in a concurrent increase of amacrine and cone cells. However, it remains unclear whether there is a cell fate switch of Math5-lineage cells in the absence of Math5 and whether MATH5 cell-autonomously regulates the differentiation of the above retinal neurons. Here, we performed a lineage analysis of Math5-expressing cells in developing mouse retinas using a conditional GFP reporter (Z/EG) activated by a Math5-Cre knock-in allele. We show that during normal retinogenesis, Math5-lineage cells mostly develop into RGCs, horizontal cells, cone photoreceptors, rod photoreceptors, and amacrine cells. Interestingly, amacrine cells of Math5-lineage cells are predominately of GABAergic, cholinergic, and A2 subtypes, indicating that Math5 plays a role in amacrine subtype specification. In the absence of Math5, more Math5-lineage cells undergo cell fate conversion from RGCs to the above retinal cell subtypes, and occasionally to cone-bipolar cells and Müller cells. This change in cell fate choices is accompanied by an up-regulation of NEUROD1, RXRγ and BHLHB5, the transcription factors essential for the differentiation of retinal cells other than RGCs. Additionally, loss of Math5 causes the failure of early progenitors to exit cell cycle and leads to a significant increase of Math5-lineage cells remaining in cell cycle. Collectively, these data suggest that Math5 regulates the generation of multiple retinal cell types via different mechanisms during retinogenesis

Multiwavelength Analysis of a Nearby Heavily Obscured AGN in NGC 449

We presented the multiwavelength analysis of a heavily obscured active galactic nucleus (AGN) in NGC 449. We first constructed a broadband X-ray spectrum using the latest NuSTAR and XMM-Newton data. Its column density ($\simeq 10^{24} \rm{cm}^{-2}$) and photon index ($\Gamma\simeq 2.4$) were reliably obtained by analyzing the broadband X-ray spectrum. However, the scattering fraction and the intrinsic X-ray luminosity could not be well constrained. Combined with the information obtained from the mid-infrared (mid-IR) spectrum and spectral energy distribution (SED) fitting, we derived its intrinsic X-ray luminosity ($\simeq 8.54\times 10^{42} \ \rm{erg\ s}^{-1}$) and scattering fraction ($f_{\rm{scat}}\simeq 0.26\%$). In addition, we also derived the following results: (1). The mass accretion rate of central AGN is about $2.54 \times 10^{-2} \rm{M}_\odot\ \rm{yr}^{-1}$, and the Eddington ratio is $8.39\times 10^{-2}$; (2). The torus of this AGN has a high gas-to-dust ratio ($N_{\rm H}/A_{\rm V}=8.40\times 10^{22}\ \rm{cm}^{-2}\ \rm{mag}^{-1}$); (3). The host galaxy and the central AGN are both in the early stage of co-evolution.Comment: 12 pages, 5 figures, 3 tables, Accepted to PAS

Gene expression changes in the ventral hippocampus and medial prefrontal cortex of adolescent alcohol-preferring (P) rats following binge-like-alcohol drinking

Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including decreased hippocampal and prefrontal cortex volume and defects in memory. We used RNA sequencing to assess the effects of adolescent binge drinking on gene expression in these regions. Male adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking (three 1-hour sessions/d during the dark/cycle, 5 days/week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 to 3 g/kg/session). Ethanol significantly altered the expression of 416 of 11,727 genes expressed in the ventral hippocampus. Genes and pathways involved in neurogenesis, long-term potentiation and axonal guidance were decreased, which could relate to the impaired memory function found in subjects with adolescent alcohol binge-like exposure. The decreased expression of myelin and cholesterol genes and apparent decrease in oligodendrocytes in P rats could result in decreased myelination. In the medial prefrontal cortex, 638 of 11,579 genes were altered; genes in cellular stress and inflammatory pathways were increased, as were genes involved in oxidative phosphorylation. Overall, the results of this study suggest that adolescent binge-like alcohol drinking may alter the development of the ventral hippocampus and medial prefrontal cortex and produce long-term consequences on learning and memory, and on control of impulsive behaviors

Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking

Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5-3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system